Neoplastic transformation of normal cells into malignant tumor cells and metastatic cancer cells proceeds in a series of progressive stages. Recent molecular biological studies of tumor progression provide evidence suggesting that mutation, activation or loss of specific genes (namely proto-oncogenes, oncogenes and tumor suppressor genes) are carried out in a specific orderly sequence which correlates well with tumor progression in colon tissues (Kingler and Vogelstein, Science 251: 1366 1991), and presumably so for most other types of cancer, such as breast tumors. A typical example for certain colon tumors has been described by B. Vogelstein, and is illustrated in FIG. 1. FIG. 1, taken from Kingler and Vogelstein (supra, 1991), diagrams the series of mutations that correspond to a series of gene mutation, expression or suppression steps which characterize the progression of colon cancer. For example, the ras gene is mutated in an early step. In a later step, the P53 gene is lost or mutated. Thus, human cancers are now evaluated and characterized as a developmental genetic disease, and steps in the progression of the disease may be characterized and distinguished at a molecular level.
At present, clinical diagnosis of tumor stage usually involves detection of histological markers that operationally define benign, adenoma, carcinoma, infiltrating carcinoma and metastatic carcinoma cells. In many cases, this morphological diagnosis is known to be insufficient or misleading for prognosis and treatment of cancer patients. Molecular genetic probes and tools could be used to characterize the biochemical and molecular phenotype of tumors at different stages. This genetic information would be useful to fine-tune the identification of tumor stages and, thus, would be useful for prognosis and treatment of specific tumors. Due to the small size of early-stage tumors or other suspect tissues, it may be difficult to use direct biochemical analysis to test for molecular phenotypes.
The prior art lacks a method to characterize and stage a patient's clinical tumor sample with a reporter gene expression assay system.